Following extraperiosteal injections of saline, serum, or whole blood, the synthesis of DNA in the cells of the osteogenic layer of the femora of mice was stimulated to approximately two-thirds of the level obtained by fracture of the femora. Irrespective of the material injected, the proliferative response of the cells in the periosteum was similar. These studies have shown that neither bone fracture nor direct disruption of the periosteum is necessary to induce periosteal cell proliferation since a single extraperiosteal injection of physiological saline induces DNA synthesis.